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Transcriptional regulation induced by cAMP elevation in mouse Schwann cells.

Schmid D, Zeis T, Schaeren-Wiemers N - ASN Neuro (2014)

Bottom Line: One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1), whose mRNA expression levels were reduced in treated Schwann cells.Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage.Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix), underlining its importance during Schwann cell differentiation in vitro.

View Article: PubMed Central - PubMed

Affiliation: *Neurobiology, Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.

ABSTRACT
In peripheral nerves, Schwann cell development is regulated by a variety of signals. Some of the aspects of Schwann cell differentiation can be reproduced in vitro in response to forskolin, an adenylyl cyclase activator elevating intracellular cAMP levels. Herein, the effect of forskolin treatment was investigated by a comprehensive genome-wide expression study on primary mouse Schwann cell cultures. Additional to myelin-related genes, many so far unconsidered genes were ascertained to be modulated by forskolin. One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1), whose mRNA expression levels were reduced in treated Schwann cells. Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage. Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix), underlining its importance during Schwann cell differentiation in vitro. Comparison of samples derived from postnatal sciatic nerves and from both treated and untreated Schwann cell cultures showed considerable differences in gene expression between in vivo and in vitro, allowing us to separate Schwann cell autonomous from tissue-related changes. The whole data set of the cell culture microarray study is provided to offer an interactive search tool for genes of interest.

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GO-annotations of differentially expressed genes due to forskolin                            treatment                        Analysis of molecular functions revealed that several transcripts                            increased with forskolin are associated with cytoskeletal protein and                            actin binding. Both sets of transcripts either increased or decreased                            due to forskolin manifested association with the cellular component of                            ECM and with the plasma membrane. The term of basement membrane and                            integrin complex was exclusively enriched in forskolin-reduced                            transcripts. GO-annotation analysis of transcripts decreased with                            forskolin showed an enrichment of genes implicated in intracellular                            signaling cascade and in the MAPKK cascade. Raw data are provided as                            Supplementary Table S4 (available at http://www.asnneuro.org/an/006/an006e142add.htm).
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Figure 3: GO-annotations of differentially expressed genes due to forskolin treatment Analysis of molecular functions revealed that several transcripts increased with forskolin are associated with cytoskeletal protein and actin binding. Both sets of transcripts either increased or decreased due to forskolin manifested association with the cellular component of ECM and with the plasma membrane. The term of basement membrane and integrin complex was exclusively enriched in forskolin-reduced transcripts. GO-annotation analysis of transcripts decreased with forskolin showed an enrichment of genes implicated in intracellular signaling cascade and in the MAPKK cascade. Raw data are provided as Supplementary Table S4 (available at http://www.asnneuro.org/an/006/an006e142add.htm).

Mentions: The usage of GO (gene ontology) annotations allows analyzing differentially expressed transcripts by means of a controlled vocabulary, in respect to the categories of cellular components, molecular functions and biological processes (Figure 3 and Supplementary Table S4; available at http://www.asnneuro.org/an/006/an006e142add.htm). Ana-lysis of molecular functions revealed that forskolin-induced transcripts were associated with cytoskeletal protein binding, actin binding and ECM binding, as well as with cytokine and chemokine activity. Investigation of GO-annotations on cellular components revealed a high association of both sets of transcripts with the ECM, the extracellular region and the plasma membrane. Furthermore, genes with reduced mRNA expression levels in treated cells showed enrichment for the annotations basement membrane and integrin complex. Analysis of the category ‘biological processes’ revealed that increased and decreased transcripts were often associated with cell adhesion, migration and proliferation, as well as with cell–cell signaling. The term of MAPKKK (MAPK kinase kinase) cascade, which is implicated in Schwann cell dedifferentiation (Harrisingh et al., 2004), was detected exclusively in the set of transcripts with reduced expression due to forskolin treatment.


Transcriptional regulation induced by cAMP elevation in mouse Schwann cells.

Schmid D, Zeis T, Schaeren-Wiemers N - ASN Neuro (2014)

GO-annotations of differentially expressed genes due to forskolin                            treatment                        Analysis of molecular functions revealed that several transcripts                            increased with forskolin are associated with cytoskeletal protein and                            actin binding. Both sets of transcripts either increased or decreased                            due to forskolin manifested association with the cellular component of                            ECM and with the plasma membrane. The term of basement membrane and                            integrin complex was exclusively enriched in forskolin-reduced                            transcripts. GO-annotation analysis of transcripts decreased with                            forskolin showed an enrichment of genes implicated in intracellular                            signaling cascade and in the MAPKK cascade. Raw data are provided as                            Supplementary Table S4 (available at http://www.asnneuro.org/an/006/an006e142add.htm).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834722&req=5

Figure 3: GO-annotations of differentially expressed genes due to forskolin treatment Analysis of molecular functions revealed that several transcripts increased with forskolin are associated with cytoskeletal protein and actin binding. Both sets of transcripts either increased or decreased due to forskolin manifested association with the cellular component of ECM and with the plasma membrane. The term of basement membrane and integrin complex was exclusively enriched in forskolin-reduced transcripts. GO-annotation analysis of transcripts decreased with forskolin showed an enrichment of genes implicated in intracellular signaling cascade and in the MAPKK cascade. Raw data are provided as Supplementary Table S4 (available at http://www.asnneuro.org/an/006/an006e142add.htm).
Mentions: The usage of GO (gene ontology) annotations allows analyzing differentially expressed transcripts by means of a controlled vocabulary, in respect to the categories of cellular components, molecular functions and biological processes (Figure 3 and Supplementary Table S4; available at http://www.asnneuro.org/an/006/an006e142add.htm). Ana-lysis of molecular functions revealed that forskolin-induced transcripts were associated with cytoskeletal protein binding, actin binding and ECM binding, as well as with cytokine and chemokine activity. Investigation of GO-annotations on cellular components revealed a high association of both sets of transcripts with the ECM, the extracellular region and the plasma membrane. Furthermore, genes with reduced mRNA expression levels in treated cells showed enrichment for the annotations basement membrane and integrin complex. Analysis of the category ‘biological processes’ revealed that increased and decreased transcripts were often associated with cell adhesion, migration and proliferation, as well as with cell–cell signaling. The term of MAPKKK (MAPK kinase kinase) cascade, which is implicated in Schwann cell dedifferentiation (Harrisingh et al., 2004), was detected exclusively in the set of transcripts with reduced expression due to forskolin treatment.

Bottom Line: One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1), whose mRNA expression levels were reduced in treated Schwann cells.Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage.Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix), underlining its importance during Schwann cell differentiation in vitro.

View Article: PubMed Central - PubMed

Affiliation: *Neurobiology, Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.

ABSTRACT
In peripheral nerves, Schwann cell development is regulated by a variety of signals. Some of the aspects of Schwann cell differentiation can be reproduced in vitro in response to forskolin, an adenylyl cyclase activator elevating intracellular cAMP levels. Herein, the effect of forskolin treatment was investigated by a comprehensive genome-wide expression study on primary mouse Schwann cell cultures. Additional to myelin-related genes, many so far unconsidered genes were ascertained to be modulated by forskolin. One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1), whose mRNA expression levels were reduced in treated Schwann cells. Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage. Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix), underlining its importance during Schwann cell differentiation in vitro. Comparison of samples derived from postnatal sciatic nerves and from both treated and untreated Schwann cell cultures showed considerable differences in gene expression between in vivo and in vitro, allowing us to separate Schwann cell autonomous from tissue-related changes. The whole data set of the cell culture microarray study is provided to offer an interactive search tool for genes of interest.

Show MeSH